| First Author | Bu Y | Year | 2018 |
| Journal | Diabetes | Volume | 67 |
| Issue | 9 | Pages | 1761-1772 |
| PubMed ID | 29945891 | Mgi Jnum | J:264587 |
| Mgi Id | MGI:6196466 | Doi | 10.2337/db17-1201 |
| Citation | Bu Y, et al. (2018) Insulin Regulates Lipolysis and Fat Mass by Upregulating Growth/Differentiation Factor 3 in Adipose Tissue Macrophages. Diabetes 67(9):1761-1772 |
| abstractText | Previous genetic studies in mice have shown that functional loss of activin receptor-like kinase 7 (ALK7), a type I transforming growth factor-beta receptor, increases lipolysis to resist fat accumulation in adipocytes. Although growth/differentiation factor 3 (GDF3) has been suggested to function as a ligand of ALK7 under nutrient-excess conditions, it is unknown how GDF3 production is regulated. Here, we show that a physiologically low level of insulin converts CD11c(-) adipose tissue macrophages (ATMs) into GDF3-producing CD11c(+) macrophages ex vivo and directs ALK7-dependent accumulation of fat in vivo. Depletion of ATMs by clodronate upregulates adipose lipases and reduces fat mass in ALK7-intact obese mice, but not in their ALK7-deficient counterparts. Furthermore, depletion of ATMs or transplantation of GDF3-deficient bone marrow negates the in vivo effects of insulin on both lipolysis and fat accumulation in ALK7-intact mice. The GDF3-ALK7 axis between ATMs and adipocytes represents a previously unrecognized mechanism by which insulin regulates both fat metabolism and mass. |
